In Vitro Activities of Iodonium Salts against Oral and Dental Anaerobes

Abstract

The comparative in vitro activities of 11 iodonium salt compounds, 0.12% chlorhexidine, and four antimicrobial agents against 322 anaerobic and fastidious potential dental and periodontal bacterial pathogens were studied. Iodonium salts 3, 4, 5, 9, and 10 had in vitro activities comparable to that of chlorhexidine against most isolates. These compounds may be suitable for incorporation into an oral mouthwash.Biodiversity studies of subgingival plaque estimate that more than 400 different species may colonize the subgingival region (7,8,12), with approximately 20% of these species not being cultivable by current methods. These microbes occupy microbiologically different ecological niches in the oral cavity. Subsets of these isolates, still not fully defined, are potentially pathogenic and cause a variety of orally related diseases. Periodontal diseases, including gingivitis and periodontitis, are chronic conditions that develop as a result of bacterial accumulations (plaque) on the teeth and gingivae. Their prevalence increases with increasing age, and approximately 50% of adults in the United States have gingivitis around three to four teeth at any given time. Moreover, 30% develop periodontitis and approximately 3% have advanced or aggressive periodontitis (1).Gingivitis is of polymicrobial origin and can be reversed with good oral hygiene. Periodontitis is a major cause of tooth loss in humans. These diseases are associated with an alteration of the healthy oral flora and an increase in the isolation of periodontal pathogenic species, especially anaerobic bacteria such as Bacteroides forsythus (Tannerella forsythensis), Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, and a variety of uncultivable spirochetes (1,8,13). Therapies include adherence to good oral hygiene, dental procedures, and the administration of topical and oral antimicrobial agents.Another adjunctive, popular approach is consumer selfadministration of mouthwashes which contain a variety of ingredients to kill oral bacteria, including alcohol, cetylpyridinium chloride, zinc chloride, benzoic acid, benzalkonium chloride, eucalyptus oil, and thymol. Chlorhexidine gluconatecontaining mouthwashes (e.g., Perio Rx) are available with medical or dental prescriptions. These have the ability to bind and penetrate plaque biofilm and prevent bacterial aggregation, slow multiplication, and extract endotoxins.Iodonium salts are organic cations with profound and wideranging physiological actions that are based on the inhibition of pyrroloquinoline quinone (or methoxatin 1), a bis(quinone) tricarboxylic acid that is an organic cofactor in the biological redox cycling process (2). These activities include mitochondrial toxicity causing blockage of gluconeogenesis, inhibition of the respiratory burst in stimulated neutrophils, and the inhibition of nitric oxide synthase (2) and broad-spectrum inhibitory activity against bacteria, fungi, yeasts, and small viruses (patent disclosure). Preliminary data (supplied by Ch...

Synthesis of fluoro-functionalized diaryl-λ3-iodonium salts and their cytotoxicity against human lymphoma U937 cells

“…On the other hand, there are only fragmented reports on the biological activity of diaryliodonium salts [ 44 – 49 ]. Goldstein et al [ 45 ] and Doroshow et al [ 46 ] reported that some diaryliodonium salts show effective antimicrobial and NOX inhibitor activity, respectively. Several aryliodonium salts, aryliodonium ylides, and (diacyloxyiodo)arenes were also examined for their antibacterial activities against ice nucleation active Pseudomonas syringae, and aryliodonium salts, especially those with electron-withdrawing groups, exhibit higher antibacterial activities [ 49 ].…”

Synthesis, Surface Activity, and Antimicrobial Efficacy of Diaryliodonium Salt‐Derived Amphiphiles

“…Bearing two benzene rings as the hydrophobic moiety, the synthesized hypervalent iodine salts would disrupt bacterial cell membrane in the same manner, causing the disintegration of the cell membrane, leakage of cytoplasmic components, and subsequent death. The introduction of a long ether chain has not only enhanced the hydrophilicity of the diaryliodonium salts resulting in a better hydrophilic–lipophilic balance (Goldstein et al, ) but also facilitated the interaction between the amphiphilic molecule and bacterial cell membrane via the formation of hydrogen bonds. As suggested by the structural descriptors predicting antiseptic efficacy summarized in Cronin et al’s () work, hydrogen bonds help to strengthen the interaction between antibacterial compounds and the outer cell membrane, further contributing to enhanced antibacterial efficacy.…”

“…We have used three synthetic routes to obtain 19 diaryliodonium salts, and all of them gave high yield, ideal purity, and easy handling (Bielawski et al, ; Matsuzaki et al, ; Petersen et al, ). To address the poor water solubility issue of the fluorinated diaryliodonium salts (Goldstein et al, ), a long ether chain containing three ethoxy groups was added to one of the benzene rings of the scaffold. The purity of the 19 diaryliodonium salts was roughly determined by the experimental phenomenon that only one spot was observed on thin layer chromatography (TLC) measurements when using various developing solvents.…”

“…It was suggested that hypervalent iodonium salts would exhibit a variety of inhibitive actions on cells owing to their inhibition of pyrroloquinoline quinone, a cofactor occurring in the redox cycle process (Gallop et al, ). In 2004, Goldstein et al () evaluated the antimicrobial ability of 11 hypervalent iodonium salts and found that five of them possessed moderate to good antimicrobial efficacy against a set of anaerobic bacterial pathogens.…”

“…Iodonium salts synthesized by Goldstein et al () exhibited great antimicrobial efficacy with minimum inhibition concentration values between 128 and >512 μg mL −1 when applied to different bacterial strains. The diaryliodonium salts synthesized in this work showed the same level of antiseptic ability, keeping the lethality rate R above 50% at the concentration of 400 μg mL −1 after 24 h of cultivation (see Supporting Information).…”